RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Sintilimab plus autologous NK cells as second-line treatment for advanced non-small-cell lung cancer previous treated with platinum-containing chemotherapy.
Sintilimab plus autologous NK cells as second-line treatment for advanced non-small-cell lung cancer previous treated with platinum-containing chemotherapy.
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这项初步研究(NCT03958097; https://www.ClinicalTrials.gov/ct2/show/NCT03958097)旨在评估PD-1抗体联合自体NK细胞治疗一线含铂化疗失败的IIIB/IIIC或IV期非小细胞肺癌(NSCLC)患者的疗效和安全性。所有患者每3周接受信迪利单抗200mg和3×10 9 NK细胞治疗。共入组20例患者,中位随访时间为22.6个月。中位PFS为11.6个月,ORR为45%。中位OS为17.7个月,6个月OS率和12个月OS率分别为95.0%和80.0%。未观察到预期外的不良事件。2例患者报告了3级不良事件(高甘油三酯血症、中性粒细胞减少和肌酸激酶升高)。自体NK细胞未给ICI治疗增加额外的不良事件。在一线治疗失败的晚期驱动基因阴性NSCLC中,自体NK联合信迪利单抗显示出有前景的抗肿瘤活性和可接受的安全性。
This pilot study (NCT03958097; https://www. clinicaltrials. gov/ct2/show/NCT03958097) was aimed to evaluate the efficacy and safety of PD-1 antibody combined autologous NK cells in the treatment of patients with stage IIIB/IIIC or IV non-small-cell lung cancer (NSCLC) who failed the first-line platinum-based chemotherapy. All patients received both sintilimab 200mg and 3×10 9 NK cells every 3 weeks. 20 patients were enrolled, median follow up time was 22. 6 months. The median PFS was 11. 6 months, ORR was 45%.
Median OS was 17. 7 months, 6-month OS rate and 12-month OS rate was 95. 0% and 80. 0%. Unexpected adverse events were not observed. 2 patients reported grade 3 adverse events (hypertriglyceridemia, neutropenia and increased creatine kinase). The autologous NK cells did not add extra adverse events to the ICI treatment. Autologous NK plus sintilimab showed promising antitumor activity and an acceptable safety profile in advanced driven-mutation negative NSCLC who failed on the first line treatment.
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